P1150: REAL WORLD DATA ON BORTEZOMIB-BASED THERAPY IN WALDENSTRÖM’S MACROGLOBULINAEMIA: EFFECTIVE EVEN IN MULTIPLY TREATED PATIENTS INCLUDING PRIOR BTK-INHIBITORS
Authors: E. Uppal, J. Khwaja, A. Rismani, C. Kyriakou, S. D’Sa
Journal: HemaSphere (2022)

Background: Waldenström macroglobulinemia (WM) is an indolent lymphoma with a prolonged disease course which typically follows a remitting and relapsing trajectory, eventually leading to treatment resistance. Several treatment options exist including Bruton tyrosine kinase inhibitors (BTKi), rituximab-containing regimens, and bortezomib-containing regimens. Treatment selection is based on patient performance status, disease characteristics, drug tolerability and availability. Aims: To assess the effectiveness and tolerability of bortezomib-based regimens in WM. Methods: Data for patients who had Bortezomib-containing regimens between 2010 and 2021 from 6 centres in the United Kingdom were retrospectively reviewed. Data was acquired from the WMUK Rory Morrison Registry. Research ethics approval was obtained. Results: Thirty-four patients were identified: 32/34 had Bortezomib-containing regimens once and 2/34 had >1 Bortezomib-containing regimens on separate occasions, giving a total of 38 subcutaneous Bortezomib-containing regimens administered at bi-weekly and weekly schedules. Median age was 62 years (37-87), with a median of 2 prior lines of therapy (0-7), at a median duration of 49.6 months from date of WM diagnosis (0.7-422). 5 patients received a prior BTKi, with the Bortezomib regimen prescribed following a median of 3 prior lines of therapy (2-5) in this group. Patients who were treated at first line had elected for non-chemotherapy regimens. Median performance status was 1 (0-2) in 23 evaluable patients. The median M-protein at initiation was 34.5g/l (8-60) with bone marrow infiltration 70%, and haemoglobin 94g/l (88-107). A median of 5 cycles (1-8) were delivered and 65% (13/20) received a dose of 1.6mg/m2 and 35% (7/20) received 1.3mg/m2. Grade (G) 1 to 2 neuropathy occurred in 19% (5/26) of evaluable patients but did not result in treatment cessation in any case. Six of 25 (24%) needed a dose reduction, the majority due to G1-2 neuropathy (67%; 4/6). Gastrointestinal disturbance occurred in 12% (3/26) patients, 1 required admission with G4 diarrhoea and remaining cases were G1. Of 34 evaluable cases, major response rate (≥ PR) was 74% (5 CR, 6 VGPR, 14 PR). 62% (8/13) of patients receiving 1.6mg/m2 achieved a major response and 86% (6/7) of those who received 1.3mg/m2. Three of 5 patients who had prior BTKi achieved PR, 1 MR, 1 SD. Two patients had treatment discontinued due refractory disease. The overall median time to best response was 81 days from end of treatment. Six of 19 (26%) evaluable patients achieved best response during therapy. Two patients died during treatment due to infection (COVID; respiratory sepsis), not attributable to disease relapse. Eighteen patients (60%; 18/30) had treatment after bortezomib regimens at a median of 5.3 months (0-75) and are alive. Median follow up was 30 months (1-111). Twenty-one evaluable patients (72%; 21/29) were alive at the end of follow up. Image:Summary/Conclusion: This retrospective real-world analysis shows that bortezomib-containing regimens have utility in WM with effective major response rates even in those with multiple prior lines of therapy and heavy marrow infiltration including BTKi failures. Lower bortezomib doses are effective, and GI and neurotoxicity are manageable with dose reductions but no treatment discontinuations in this real-world cohort indicating an acceptable safety profile.